Effect of bombesin on impairment of upper respiratory tract immunity induced by total parenteral nutrition

P. G. Janu, K. A. Kudsk, J. Li and K. B. Renegar
Department of Surgery, University of Tennessee at Memphis, USA.

OBJECTIVE: To determine the effect of the neuropeptide bombesin on total parenteral nutrition-induced impairment of upper respiratory tract immunity. DESIGN: Randomized, controlled trial. PARTICIPANTS: Thirty-six adult male Institute for Cancer Research mice weighing 25 to 35 g. INTERVENTIONS: Mice were inoculated intranasally with H1N1 virus. At 3 weeks, mice were randomized to receive chow plus intravenous saline (n = 12), intravenous total parenteral nutrition (n = 12), or intravenous total parenteral nutrition plus bombesin (n = 12) administered 3 times daily at 15 micrograms/kg. After 5 days, mice were rechallenged with intranasal virus and killed at 40 hours to determine viral shedding from the respiratory tract; normal convalescent mice do not shed virus because of intact IgA-mediated mechanisms. MAIN OUTCOME MEASURES: Viral shedding was determined by collection of nasal secretions. Samples were diluted and incubated with a suspension of Madin-Darby canine kidney cells. Viral growth was determined by hemagglutination. RESULTS: Body weight was similar between the total parenteral nutrition and bombesin groups; however, both were significantly lower than that in the chow group (P < .05). After 6 days of feeding, no mice in the chow group shed virus, compared with 6 (50%) of the mice in the total parenteral nutrition group. Of the mice in the bombesin group, only 1 was positive for viral shedding. The total parenteral nutrition group showed increased viral shedding compared with both the chow group (P < .01) and the bombesin group (P < .05). CONCLUSIONS: Exogenous administration of bombesin reversed the total parenteral nutrition-associated impairment of upper respiratory tract immunity to an IgA-mediated infectious challenge. These observations support the concept of a common mucosal immune system, since neuropeptides are endogenous to the gastrointestinal and respiratory tracts. Hormonal modulation of immunity is a promising avenue of treatment for patients who require total parenteral nutrition.